title: Improvement of daptomycin production in Streptomyces roseosporus through the acquisition of pleuromutilin resistance.
abstract: Daptomycin, a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus, displays potent activity against a variety of gram-positive pathogens. There is a demand for generating high-producing strains for industrial production of this valuable antibiotic. Ribosome engineering is a powerful strategy to enhance the yield of secondary metabolites. In this study, the effect of a diterpenoid antibiotic pleuromutilin resistance mutation on daptomycin production was assessed. Spontaneous pleuromutilin-resistant derivatives of S. roseosporus were isolated. Sequencing of rplC locus (encoding the ribosomal protein L3) showed a point mutation at nt 455, resulting in the substitution of glycine with valine. G152V mutants showed increased production of daptomycin by approximately 30% in comparison with the wild-type strain. Its effect on daptomycin production was due to enhanced gene transcription of the daptomycin biosynthetic genes. In conclusion, pleuromutilin could be used as a novel ribosome engineering agent to improve the production of desired secondary metabolites.
authors.affiliation: Institute of Modern Biopharmaceuticals, School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Li
authors.forename: Tingmei
authors.initials: T
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Huang
authors.forename: Changhua
authors.initials: C
authors.lastname: Hu
authors.forename: Guojian
authors.initials: G
authors.lastname: Liao
mesh_terms: D017576:Daptomycin / Q000096:biosynthesis*; D004224:Diterpenes / Q000008:administration & dosage / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005818:Genetic Engineering; D009154:Mutation; D011083:Polycyclic Compounds; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D000097567:Pleuromutilins
chemical_list: D017576:Daptomycin; D004224:Diterpenes; D011083:Polycyclic Compounds; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D000097567:Pleuromutilins